A cell fitness selection model for neuronal survival during development

Wang Y, Wu H, Fontanet P, Codeluppi S, Akkuratova N, Petitpré C, Xue-Franzén Y, Niederreither K, Sharma A, Da Silva F, Comai G, Agirman G, Palumberi D, Linnarsson S, Adameyko I, Moqrich A, Schedl A, La Manno G, Hadjab S, Lallemend F

Nat Commun 10 (1) - [2019-12-00; online 2019-09-12]

Developmental cell death plays an important role in the construction of functional neural circuits. In vertebrates, the canonical view proposes a selection of the surviving neurons through stochastic competition for target-derived neurotrophic signals, implying an equal potential for neurons to compete. Here we show an alternative cell fitness selection of neurons that is defined by a specific neuronal heterogeneity code. Proprioceptive sensory neurons that will undergo cell death and those that will survive exhibit different molecular signatures that are regulated by retinoic acid and transcription factors, and are independent of the target and neurotrophins. These molecular features are genetically encoded, representing two distinct subgroups of neurons with contrasted functional maturation states and survival outcome. Thus, in this model, a heterogeneous code of intrinsic cell fitness in neighboring neurons provides differential competitive advantage resulting in the selection of cells with higher capacity to survive and functionally integrate into neural networks.

Bioinformatics Support for Computational Resources [Service]

Eukaryotic Single Cell Genomics (ESCG) [Service]

NGI Stockholm (Genomics Applications) [Service]

NGI Stockholm (Genomics Production) [Service]

National Genomics Infrastructure [Service]

PubMed 31515492

DOI 10.1038/s41467-019-12119-3

Crossref 10.1038/s41467-019-12119-3

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